By regulating the production of glucose, gluconeogenesis, urea synthesis and the availability of post-prandial amino acids to peripheral tissues, the liver can regulate the "traffic" of major metabolic substrates required for protein and energy balance and impact nutritional status (8-10). Therefore, it should not be surprising that cirrhosis is associated with a high prevalence of skeletal muscle atrophy. Our central hypothesis is that this loss of skeletal muscle mass occurs because the presence of cirrhosis adversely alters the normal response to feeding as well as the normal adaptation to fasting. In fact, loss of muscle mass is a ubiquitous finding in cirrhosis;a disease which is the sixth leading cause of death among both males and females ages 35-54 and results in approximately 4000 orthotopic liver transplantations annually (11-13). It should be noted that cirrhosis due to alcohol alone, and alcohol combined with hepatitis C is the most common cause of liver related death and liver transplantations in the United States. In this proposal, the term cirrhosis is used to represent alcoholic cirrhosis. Loss of skeletal muscle mass is an independent risk factor that adversely affects survival and successful liver transplantation in cirrhotic patients (14-17). Interventions to counter this complication have been instituted without strong scientific rationale, carefully measured outcomes or proven benefit. Loss of skeletal muscle mass is a potentially reversible complication of cirrhosis that adversely affects clinical outcome and worsens with increasing severity of liver disease (12,15,18,19). Skeletal muscle mass is maintained by a balance between muscle protein synthesis, protein breakdown, and satellite cell proliferation and differentiation. Each of these pathways is regulated by the canonical Akt-mTOR pathway (Figure 1)(20). Increased proteolysis as well as lower protein synthesis in patients with cirrhosis has been shown by the coinvestigator in previous studies on whole body leucine turnover (1,21). However, the specific compartment in which proteolysis is increased has not been identified. Evidence of impaired protein synthesis in the skeletal muscle is indirect (9,22,23). There is no data on the role of impaired satellite cell function in the muscle loss of cirrhosis even though this has been observed in sarcopenia of aging and in the PCA rat model (4,24). This proposal will explore the mechanism of skeletal muscle loss in stable alcoholic cirrhotic patients by assessing the contribution of the 3 major contributors of muscle mass (protein synthesis, protein degradation and satellite cells) in response to nutrient administration.